Background: As educational institutions continually strive to enhance the medical students' learning experiences and outcomes, understanding the potential impact of self-esteem on academic performance has become increasingly important. Self-esteem, encompassing an individual's overall perception of their self-worth and capabilities, plays a pivotal role in shaping various aspects of students' lives, including their motivation, resilience, and overall well-being. Objective: To explore the relationship between levels of self-esteem with GPA among the medical students at Muhammad Medical and Dental College. Study Design: Cross-sectional descriptive study. Settings: Muhammad Medical College, Mirpurkhas Pakistan. Duration: 3 months from June-August 2018. Methods: Medical and dental under graduate students from multiple academic years of either age and gender were included. Self-esteem was measured using a validated self-report questionnaire like the Rosenberg Self-Esteem Scale. It gauges a person's self-perception by considering both positive and negative self-feelings. Questionnaires were administered to participants in a controlled and private setting, ensuring comfort and privacy. All the information was entered and analyzed by using SPSS version 26. Results: A total of 130 medical students were studied; with the majority falling in the 18-20 and 21-23 age of age groups, accounting for 36.9% and 36.2% of the cases, respectively. Most of the cases 49.20% had high self-esteem level, 47.70% cases had normal self-esteem level, while 3.10% cases low level self-esteem. The level of self-esteem was significantly influenced by the age of the students, their academic year, and GPA categories (p=0.0.05). Overall, a positive correlation (correlation coefficient of 0.271) between self-esteem and GPA suggests that higher self-esteem tends to be associated with better academic performance (pvalue=0.002). Conclusion: It was concluded that self-esteem significantly corelated with academic achievement among medical students. The findings strongly indicate that a high level of self-esteem is closely associated with superior academic performance.